Since the advent of new therapies for childhood malignancies, most pediatric cancer patients survive their disease. However, these patients encounter other long term problems in the years that follow their original diagnosis and treatment. Of these problems, growth failure often occurs early during treatment and can result in severe short stature subsequently. The cause of the growth failure during the period of cancer treatment and immediately following treatment is not clear. Although growth hormone deficiency, glucocorticoid treatment, cachexia of malignancy and the systemic toxicities of chemotherapy and/or irradiation have been implicated, prospective studies evaluating these potential factors have not been done. Certainly, the growth hormone - insulin-like growth factor (GH-IGF) axis has not been thoroughly evaluated prospectively. Recent data indicative that brain tumors, leukemias and solid organ tumors produce IGFs, IGF binding proteins (IGFBPs), and IGFBP proteases, suggest that cancer may also directly perturb the IGF axis in addition to precipitating GH deficiency. The hypothesis proposed here is that the growth failure during and immediately following cancer treatment is a result of perturbations of the GH-IGF axis. This hypothesis can be tested by a complete and inclusive laboratory assessment of the GH-IGF axis which will include measuring GH, GHBP, IGF-I, IGF-II, IGFBP-1, -2, and, -3 by radioimmunoassay (RIA), IGFBPs and their fragments by the western ligand blot and immunoblot techniques, and IGFBP protease activity before, during and following cancer treatment. Correlations will include auxologic measurements, as well as measures of nutrition (weight, dietary history and skinfold thickness), illness, infections, GI symptoms, location of tumor, the type of cancer treatment and tumor response to therapy. We believe that identifying the specific perturbations in the GH-IGF axis will allow for a more rational approach to assessing growth failure in children surviving pediatric cancer and more effective growth promoting therapy in these children.